The present invention relates to a new pharmaceutical formulation of 1-[5-[(aminoiminomethyl)amino]-1-oxo-2-[[(1,2,3,4-tetrahydro-3-methyl-8-quinolinyl)sulfonyl]amino]pentyl]-4-methyl-2-piperidinecarboxylic acid hydrate, commonly known by the generic name “argatroban.” Argatroban is a synthetic direct thrombin inhibitor derived from L-arginine and is a useful anti-coagulant agent.
Argatroban is considered slightly to very slightly soluble in water according to the USP classification of solutes, with solubility on the order of 0.8 to 0.9 mg/mL. It is also both light and heat-sensitive and tends to degrade unless stabilized. Argatroban is commercially available in concentrated form in an aseptically-filled vial containing, per mL, 100 mg argatroban, 750 mg D-sorbitol and 1000 mg dehydrated alcohol. When administered to a patient, this formulation is diluted to a concentration of 1.0 mg/mL in an admixture diluent solution containing an osmotic agent such as sodium chloride or dextrose (c.f. U.S. Pat. No. 5,214,052).
Other formulations of argatroban are described in U.S. Pat. Nos. 5,679,690 and 6,087,375, European Patent Applications 0,565,897 A1 and 0,621,036 A1 and WO 2005/009361 A2.